Sumoylation pathway is required to maintain the basal breast cancer subtype

Maria V Bogachek; Yizhen Chen; Mikhail V Kulak; George W Woodfield; Anthony R Cyr; Jung M Park; Philip M Spanheimer; Yingyue Li; Tiandao Li; Ronald J Weigel

doi:10.1016/j.ccr.2014.04.008

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Sumoylation pathway is required to maintain the basal breast cancer subtype

Journal article

Open access

Peer reviewed

Sumoylation pathway is required to maintain the basal breast cancer subtype

Maria V Bogachek, Yizhen Chen, Mikhail V Kulak, George W Woodfield, Anthony R Cyr, Jung M Park, Philip M Spanheimer, Yingyue Li, Tiandao Li and Ronald J Weigel

Cancer cell, Vol.25(6), pp.748-761

06/16/2014

DOI: 10.1016/j.ccr.2014.04.008

PMCID: PMC4096794

PMID: 24835590

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https://doi.org/10.1016/j.ccr.2014.04.008View

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Abstract

The TFAP2C/AP-2γ transcription factor regulates luminal breast cancer genes, and loss of TFAP2C induces epithelial-mesenchymal transition. By contrast, the highly homologous family member, TFAP2A, lacks transcriptional activity at luminal gene promoters. A detailed structure-function analysis identified that sumoylation of TFAP2A blocks its ability to induce the expression of luminal genes. Disruption of the sumoylation pathway by knockdown of sumoylation enzymes, mutation of the SUMO-target lysine of TFAP2A, or treatment with sumoylation inhibitors induced a basal-to-luminal transition, which was dependent on TFAP2A. Sumoylation inhibitors cleared the CD44(+/hi)/CD24(-/low) cell population characterizing basal cancers and inhibited tumor outgrowth of basal cancer xenografts. These findings establish a critical role for sumoylation in regulating the transcriptional mechanisms that maintain the basal cancer phenotype.

Animals

Breast Neoplasms - classification

Breast Neoplasms - drug therapy

Breast Neoplasms - genetics

Breast Neoplasms - metabolism

Cell Line, Tumor

Female

Gene Expression Profiling

Gene Expression Regulation, Neoplastic

Humans

MCF-7 Cells

Mice

Mice, Nude

Multigene Family

Neoplasms, Basal Cell - classification

Neoplasms, Basal Cell - drug therapy

Neoplasms, Basal Cell - genetics

Neoplasms, Basal Cell - metabolism

Small Ubiquitin-Related Modifier Proteins - genetics

Small Ubiquitin-Related Modifier Proteins - metabolism

Sumoylation - drug effects

Sumoylation - genetics

Transcription Factor AP-2 - genetics

Transcription Factor AP-2 - metabolism

Transcriptional Activation

Transfection

Treatment Outcome

Xenograft Model Antitumor Assays

Details

Title: Subtitle: Sumoylation pathway is required to maintain the basal breast cancer subtype
Creators: Maria V Bogachek - University of Iowa
Yizhen Chen - University of Iowa
Mikhail V Kulak - University of Iowa
George W Woodfield - University of Iowa
Anthony R Cyr - University of Iowa
Jung M Park - University of Iowa
Philip M Spanheimer - University of Iowa
Yingyue Li - University of Iowa
Tiandao Li - Washington University in St. Louis
Ronald J Weigel - University of Iowa
Resource Type: Journal article
Publication Details: Cancer cell, Vol.25(6), pp.748-761
DOI: 10.1016/j.ccr.2014.04.008
PMID: 24835590
PMCID: PMC4096794
ISSN: 1535-6108
eISSN: 1878-3686
Grant note: R01CA109294 / NCI NIH HHS T32 CA078586 / NCI NIH HHS T32 CA148062 / NCI NIH HHS P30 CA086862 / NCI NIH HHS R01 CA109294 / NCI NIH HHS T32CA148062 / NCI NIH HHS
Language: English
Date published: 06/16/2014
Academic Unit: Molecular Physiology and Biophysics; Anatomy and Cell Biology; Surgery; Biochemistry and Molecular Biology
Record Identifier: 9984284324402771

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